 The study shows that deletion of SIRT-2 in mice improves cardiac function after ischemia reperfusion and pressure overload, suggesting that SIRT-2 exerts maladaptive effects in the heart in response to stress. Mechanistic studies suggest that SIRT-2 modulates cellular levels and activity of nuclear factor, erythroid derived 2, like 2, which results in reduced expression of antioxidant proteins. Treatment of mouse hearts with a specific SIRT-2 inhibitor reduces cardiac size and attenuates cardiac hypertrophy in response to pressure overload, providing a novel avenue for the treatment of these disorders. This article was authored by Xiao Yongyang, Xiong Chenchang, Yuki Tatakoshi, and others.